Abstract

AIMS:

Objective methods to monitor statin adherence are needed. We have established a liquid chromatography-tandem mass spectrometry assay for quantification of atorvastatin and its metabolites in blood. This study aimed to develop an objective drug exposure variable with cut-off values to discriminate among adherence, partial adherence and non-adherence to atorvastatin therapy in patients with coronary heart disease.

METHODS:

Twenty-five patients treated with atorvastatin 10 mg (N=5), 20 mg (N=6), 40 mg (N=7) and 80 mg (N=7) participated in a directly observed atorvastatin therapy (DOT) study to confirm baseline adherence. After the DOT, half of the patients (test-group) were instructed to stop taking atorvastatin and return for blood sample collection the subsequent 3 days. Levels of atorvastatin and metabolites were compared between the test-group and the adherent control group.

RESULTS:

The sum of parent drug and all measured primary metabolites correlated well with the atorvastatin dose administered (Spearman's rho=0.71, 95% CI 0.44 to 0.87). The dose-normalized atorvastatin plus metabolites concentrations completely separated the partially adherent test-group from the controls at 0.18 (nmol/L)/mg after 3 days without atorvastatin. To reduce the risk of misinterpreting adherent patients as partially adherent, a corresponding cut-off at 0.10 (nmol/L)/mg is proposed. A metabolite level of 2-OH atorvastatin acid <0.014 nmol/L provided the optimal cut-off for non-adherence.

CONCLUSION:

A direct method to discriminate among adherence, partial adherence and non-adherence to atorvastatin therapy in patients with coronary heart disease has been developed. This tool may be important for novel studies on adherence and potentially useful in clinical practice.